Our research aims to develop and validate quantitative pH imaging technique, and evaluate its diagnostic utility in pathologies such as acute ischemia. Recently, it has been shown that chemical exchange saturation transfer (CEST) MRI can monitor microenvironment pH, and amide proton transfer (APT) MRI, a variant of CEST imaging, has been shown promising in imaging acute ischemic tissue damage. However, APT imaging provides only pH-weighted information, and its contrast varies with experimental conditions, and under the influence of edema, protein content and tissue relaxation time change. While on the other hand, it is of tremendous interest to develop an absolute tissue pH imaging that provide quantitative information about tissue energy metabolism. In validated, an absolute pH MRI technique may complement conventional spectroscopy-based techniques (e.g., lactate and ^V) to improve its spatiotemporal resolution. In addition, a validated non-invasive pH MRI technique may serve as a surrogate marker for altered tissue metabolic status, and hence, may eventually augment commonly used perfusion and diffusion MRI for more acute characterization of pathological tissue status. In fact, a non-invasive pH MRI technique can aid the diagnosis of a host of metabolic disorders beyond acute stroke. In the proposed research, we will 1) develop, quantitate and calibrate CEST MRI for absolute pH. 2) validate in vivo pH MRI using both global and focal ischemia aninrial stroke model. 3) test the diagnostic value of pH MRI by evaluating a new experimental therapeutic drug, acid sensing ion channel (ASIC) blockade. RELEVANCE: Non invasive pH imaging is generally an unmet need, and we propose to quantitate endogenous amide proton transfer MRI for mapping absolute tissue pH. Once verified, we will evaluate its diagnostic use in pathologies such as acute stroke.